Patients with Locked-In Syndrome (LIS) are cognitively intact but unable to move or communicate except through eye blinks or limited (vertical) eye movements. For many patients suffering from this predicament, self-initiated communication is no longer possible, and they are unable to start a conversation, ask a question, or draw caregiver attention. Having no other means of interacting with family or friends, these LIS patients lack privacy and any degree of independence. Recently, a Brain-Computer Interface (BCI) device was successfully implanted in a locked-in patient with late stage ALS. By modulating her brain signals, this patient was able to select letters and spell words. The breakthrough was that, for the first time, a BCI system performed well enough to enable use at home without the need for experts. This was published in the New England Journal of Medicine. Yet, the rate of spelling was only 2 characters per minute, which clearly needs to be improved. In this collaborative early-feasibility study between the University Medical Center Utrecht (The Netherlands), the Johns Hopkins University (Baltimore), and the Neuromodulation Research unit of Medtronic (Minneapolis), we will use a significantly improved version of the implant device to develop faster and more versatile BCI control techniques for home use. The overall goal of the research is 1) to prove that the basic functionality of this BCI is generalizable to other patients with LIS (AIM1), and 2) to expand current BCI capabilities through research along 3 avenues aiming to achieve A) multidimensional item selection (avenue ?Multiselect?) that would allow patients to choose among multiple menu options, B) 2D cursor control (avenue ?Navigate?) that would allow point-and-click use of a computer, similar to that of eye trackers for users with normal eye movements, and C) vocalization through a speech synthesizer (avenue ?Speak?) (AIM2), which would greatly enhance communication and quality of life. A total of nine LIS patients will participate for one year each, during and after which they may continue to use the BCI system at home. An additional 16 patients with electrode grids implanted for unrelated diagnostic purposes (epilepsy surgery) will be included for the development of advanced decoding algorithms, utilizing clinical 256-channel recording systems. The study will demonstrate the feasibility of providing LIS patients with an alternative means of communication, thereby moving the current state of the art in human neuroscience to the realm of clinical treatment for severe communication disorders.